The long-term objectives of this research project are to determine whether altered functioning of the central and peripheral endogenous vasopressin systems is associated with the development and maintenance of ethanol tolerance and whether depressed functioning of the angiotensin II system is associated with high oral ethanol intake. When examining whether specific endocrine systems contribute to the development of high ethanol drinking and ethanol tolerance, it is necessary to compare endocrine function in animals that differ in both of these variables. Rats of the alcohol-preferring (P) and alcohol-nonpreferring (NP) lines represent unique models for such experimentation because these two lines differ genetically in both oral ethanol intake and in the development and maintenance of ethanol tolerance. The proposed studies will examine whether arginine vasopressin (AVP) content in plasma, and the content, receptor binding, and genetic message for synthesis of AVP in discrete brain and pituitary regions differ in rats from the P and NP lines under the following conditions: I) prior to ethanol exposure (ethanol-naive), 2) following induction of acute (2-injection) ethanol tolerance, and 3) following induction of chronic ethanol tolerance with free-choice drinking. We will also determine whether administration of AVP antagonists block the development of acute (2-injection) ethanol tolerance, chronic ethanol drinking and the development of chronic ethanol tolerance in rats of the P line. We also propose to determine whether acute and repeated exposures to ethanol alter functioning of the angiotensin system in rats of the P and NP lines and whether exogenous administration of angiotensin II reduces ethanol intake in rats of the P line. The results of the proposed studies should yield additional information regarding the importance of the central and peripheral vasopressin systems in mediating the development and maintenance of ethanol tolerance and 2) the importance of the angiotensin system in limiting ethanol intake.